Conformational plasticity of JRAB/MICAL-L2 provides “law and order” in collective cell migration

Molecular Biology of the Cell - Tập 27 Số 20 - Trang 3095-3108 - 2016
Ayuko Sakane1, S. Yoshizawa2, Masaomi Nishimura2, Yuko Tsuchiya3,4, Natsuki Matsushita5,6, Kazuhisa Miyake1, Kazuki Horikawa7, Issei Imoto8, Chiharu Mizuguchi9, Hiroyuki Saito9,10, Takato Ueno11, Sachi Matsushita6, Hisashi Haga11, Shinji Deguchi12, Kenji Mizuguchi4, Hideo Yokota2, Takuya Sasaki1
1Department of Biochemistry, Tokushima University, Tokushima 770-8503, Japan
2Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako 351-0198, Japan;
3Institute for Protein Research, Osaka University, Suita 565-0871, Japan
4National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Japan;
5Department of Biology, School of Medicine, Aichi Medical University, Aichi 480-1195, Japan;
6Translational Research Center, Ehime University Hospital, Ehime 791-0295, Japan;
7Department of Optical Imaging, Tokushima University, Tokushima 770-8503, Japan
8Department of Human Genetics, Graduate School of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan
9Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8503, Japan;
10Osaka University, Toyonaka 560-8531, Japan.
11Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo 770-8503, Japan;
12Laboratory for Mechanobiology and Bioengineering, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan

Tóm tắt

In fundamental biological processes, cells often move in groups, a process termed collective cell migration. Collectively migrating cells are much better organized than a random assemblage of individual cells. Many molecules have been identified as factors involved in collective cell migration, and no one molecule is adequate to explain the whole picture. Here we show that JRAB/MICAL-L2, an effector protein of Rab13 GTPase, provides the “law and order” allowing myriad cells to behave as a single unit just by changing its conformation. First, we generated a structural model of JRAB/MICAL-L2 by a combination of bioinformatic and biochemical analyses and showed how JRAB/MICAL-L2 interacts with Rab13 and how its conformational change occurs. We combined cell biology, live imaging, computational biology, and biomechanics to show that impairment of conformational plasticity in JRAB/MICAL-L2 causes excessive rigidity and loss of directionality, leading to imbalance in cell group behavior. This multidisciplinary approach supports the concept that the conformational plasticity of a single molecule provides “law and order” in collective cell migration.

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